Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Identifying novel mechanisms and treatment targets for irritability and aggression in psychiatric disorders

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. 1.

    Jha MK, Minhajuddin A, South C, Rush AJ, Trivedi MH. Irritability and its clinical utility in major depressive disorder: prediction of individual-level acute-phase outcomes using early changes in irritability and depression severity. Am J Psychiatry. 2019;176:358–66.

    Article  Google Scholar 

  2. 2.

    Jha MK, Minhajuddin A, Chin Fatt C, Kircanski K, Stringaris A, Leibenluft E, et al. Association between irritability and suicidal ideation in three clinical trials of adults with major depressive disorder. Neuropsychopharmacology 2020;45:2147–54.

    Article  Google Scholar 

  3. 3.

    Covington HE, 3rd, Newman EL, Leonard MZ, Miczek KA. Translational models of adaptive and excessive fighting: an emerging role for neural circuits in pathological aggression. F1000Res. 2019;8:963.

    Article  Google Scholar 

  4. 4.

    Flanigan ME, Aleyasin H, Li L, Burnett CJ, Chan KL, LeClair KB, et al. Orexin signaling in GABAergic lateral habenula neurons modulates aggressive behavior in male mice. Nat Neurosci. 2020;23:638–50.

    CAS  Article  Google Scholar 

  5. 5.

    Cherek DR, Tcheremissine OV, Lane SD, Nelson R. Psychopharmacology of human aggression: Laboratory and clinical studies. Biol Aggress. 2006:424–46.

  6. 6.

    Leibenluft E, Kircanski K. Chronic irritability in youth: a reprise on challenges and opportunities toward meeting unmet clinical needs. Child Adolesc Psychiatr Clin North Am. 2021;30:667–83.

    Article  Google Scholar 

Download references


The authors thank Kathryn Forbes, MS for administrative support.


This work was supported by the Hersh Foundation and the Center for Depression Research and Clinical Care (PI: Madhukar Trivedi) at UT Southwestern. MKJ has received contract research grants from Acadia Pharmaceuticals and Janssen Research & Development, educational grant to serve as Section Editor of the Psychiatry & Behavioral Health Learning Network, consultant fees from Eleusis Therapeutics US, Inc, and honoraria for CME presentations from North American Center for Continuing Medical Education and Global Medical Education. patent for using mTORC1 inhibitors to augment the effects of antidepressants (Aug 20, 2018). MHT has served as an adviser or consultant for Abbott Laboratories, Abdi Ibrahim, Akzo (Organon Pharmaceuticals), Alkermes, AstraZeneca, Axon Advisors, Bristol-Myers Squibb, Cephalon, Cerecor, CME Institute of Physicians, Concert Pharmaceuticals, Eli Lilly, Evotec, Fabre Kramer Pharmaceuticals, Forest Pharmaceuticals, GlaxoSmithKline, Janssen Global Services, Janssen Pharmaceutica Products, Johnson & Johnson PRD, Libby, Lundbeck, Meade Johnson, MedAvante, Medtronic, Merck, Mitsubishi Tanabe Pharma Development America, Naurex, Neuronetics, Otsuka Pharmaceuticals, Pamlab, Parke-Davis Pharmaceuticals, Pfizer, PgxHealth, Phoenix Marketing Solutions, Rexahn Pharmaceuticals, Ridge Diagnostics, Roche Products, Sepracor, Shire Development, Sierra, SK Life and Science, Sunovion, Takeda, Tal Medical/Puretech Venture, Targacept, Transcept, VantagePoint, Vivus, and Wyeth-Ayerst Laboratories; he has received grants or research support from the Agency for Healthcare Research and Quality, Cyberonics, NARSAD, NIDA, and NIMH.

Author information




Both authors contributed equally to the conceptualization of the article, literature search, writing, and revision of this manuscript. Both authors approved the final version of the paper.

Corresponding author

Correspondence to Madhukar H. Trivedi.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Jha, M.K., Trivedi, M.H. Identifying novel mechanisms and treatment targets for irritability and aggression in psychiatric disorders. Neuropsychopharmacol. (2021).

Download citation


Quick links